α-bromo-2'-methoxy-4'-methylthioacetophenone | 93276-66-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-bromo-2'-methoxy-4'-methylthioacetophenone
• 英文别名: 2-Bromo-1-[2-methoxy-4-(methylthio)phenyl]ethanone；2-bromo-1-(2-methoxy-4-methylsulfanylphenyl)ethanone
• CAS: 93276-66-5
• 化学式: C₁₀H₁₁BrO₂S
• 分子量: 275.166
• InChiKey: IGCKFGLOWPSOQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α-bromo-2'-methoxy-4'-methylthioacetophenone 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以60%的产率得到2-bromo-2'-methoxy-4'-methylsulphinylacetophenone
  参考文献：
  名称：

  Inotropic 2-arylimidazol[1,2-a]pyrimidines

  摘要：

  A series of 2-arylimidazo[1,2-a]pyrimidines has been prepared and evaluated for inotropic activity. Three of these heterocycles. ether 19, sulphide 21 and mesylate 24 displayed more potent inotropic effects in vitro than isomazole. The in vivo inotropic potencies of 4'-mesylate 24 and 4'-carboxamido analogue 23 were similar to those of isomazole and sulmazole respectively. The effects of some 'A' and 'C' ring substituents on the inotropic activities of the imidazo[1,2-a]pyrimidines were different from those on the imidazopyridines. Nevertheless the inotropic potencies of several imidazo[1.2-a]pyrimidines were closer to those of their 1H-imidazo[4,5-b]pyridine isomers than to those of the corresponding isomazole analogues. Structure-activity relationships are discussed in detail.

  DOI：

  10.1016/0223-5234(92)90004-k
• 作为产物：
  描述：

  3-氟苯酚 在 吡啶 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 三氯化铝 、 sodium hydride 、 二异丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 α-bromo-2'-methoxy-4'-methylthioacetophenone
  参考文献：
  名称：

  咪唑并[1,2-a]嘧啶和咪唑并[1,2-a]吡嗪：氮位置在正性肌力活动中的作用。

  摘要：

  充血性心力衰竭是主要的医学问题，现有药物对其提供的益处有限。最近的新实验药物，包括咪唑并[4,5-b]-和咪唑并[4,5-c]吡啶，具有正性肌力和血管舒张性。这些化合物氮位置的细微变化已显示出会显着影响效能。我们合成了一系列咪唑[4,5-b]-和-[4,5-c]吡啶类似物，它们的咪唑氮原子位于桥头位置。我们的类似物的活性再次证明了[4,5-c]吡啶与[4,5-b]吡啶相比具有更好的正性肌力。证明了咪唑并[4,5-b]吡啶与咪唑并[1,2-a]嘧啶的生物等效性以及咪唑并[4,5-c]吡啶与咪唑并[1,2-a]吡嗪的生物学等效性。此外，2- [2-甲氧基-4-（甲基亚磺酰基）苯基]咪唑[1，

  DOI：

  10.1021/jm00403a018

文献信息

• Sites of protonation in cardiotonic polyazaindolizines by NMR spectroscopy
  作者：Paul Barraclough、David Firmin、John C. Lindon、Malcolm S. Nobbs、Paul N. Sanderson、Steven Smith、Janet M. Gillam

  DOI：10.1002/mrc.1260290511

  日期：1991.5

  nitrogen heterocycles were determined by 1H and 13C NMR methods. The aryl‐substituted imidazo[1,2‐a]pyrimidine (4), 8‐methoxyimidazo[1,2‐a]pyrazine (6), imidazo[1,2‐b]pyridazine (9) and imidazo[1,2‐b][1,2,4]triazine (11) undergo protonation at the imidazo nitrogen. The imidazo[1,2‐a]pyrazine (5) protonates mainly at N‐7. In some cases differences in basicity properties between these aryl analogues and

  六种舒咪唑类似物的 pKa 值通过分光光度法测量。大多数桥头氮杂环的主要质子化位点是通过 1 H 和 13 C NMR 方法确定的。芳基取代的咪唑并[1,2-a]嘧啶(4)、8-甲氧基咪唑并[1,2-a]吡嗪(6)、咪唑并[1,2-b]哒嗪(9)和咪唑并[1,2] ‐b][1,2,4]triazine (11) 在咪唑氮上发生质子化。咪唑并[1,2-a] 吡嗪 (5) 主要在 N-7 处质子化。在某些情况下，已经观察到这些芳基类似物和桥头杂环之间的碱性特性存在差异。
• Aryl derivatives of heterobicyclic compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0166609A2

  公开（公告）日：1986-01-02

  The invention relates to use of compounds of formula (I) wherein n is 1, 2 or 3; m is 0, 1, 2 or 3; any one of A', A2 and A3 is nitrogen and the other two are CH; R' groups are independently selected from those specified in (a) and (b) below, namely: (a) cyano, hydroxy, groups of formula -S(O)xRa in which x is 0, 1 or 2 and Ra is a C1-4 alkyl group and groups of formula -ORb in which Rb is allyl or a C1-4 alkyl group, which alkyl group is optionally substituted by one or more radicals selected from halo, C1-4 alkoxy and groups of formula -S(O)xRa in which x and Ra are as defined above; (b) C1-4 alkanoyl, C1-4 alkanoylamino, 2-methyl-1,3-dioxalan-2-yl, sulphamoyl, N-C1-4 alkylsulphamoyl, N, N-di-C1-4 alkylsulphamoyl, C1-4 alkylsulphonyloxy, C1-4 alkylsulphonylamino, aminosulphonyloxy, N-C1-4 alkylaminosulphonyloxy, N,N-di-C1-4 alkylaminosulphonyloxy, ureido, 3-C1-4 alkylureido, 3,3-di-C1-4 alkylureido, aminosulphonylamino, (C1-4 alkylaminosulphonyl)amino, (di-C1-4 alkylaminosulphonyl)-animo, carboxy, carboxylic derivatives (selected from carbamoyl, N-C1-4 alkylcarbamoyl, N, N-di-C1-4 alkylcarbamoyl, carboxylic acid halides, C1-4 alkoxycarbonyl, hydroxy-C1-4 alkoxycarbonyl and hydroxymethylene) and groups of formula -ORc in which Re is a straight or branched aliphatic moiety having 1 to 4 carbon atoms, optionally substituted by one or more radicals independently selected from halo, C1-4 alkoxy and groups of formula -S(O)xRa in which x and Ra are as defined above, provided that R° is not a group as defined for Rb above; R2 is selected from hydrogen, halo, amino, hydroxy, C1-4 alkyl and C1-4 alkoxy; R3 groups are independently selected from halo, carboxy, amino, C1-4 alkylamino hydroxy, C1-4 alkoxy, hydroxy-C1-4 alkoxy, C1-4 alkylthio and C1-4 alkylsulphonyloxy; provided that when R2 is hydrogen and either m is 0 or m is 1 and R3 represents halo, then at least one R' group must be selected from (b) above; and physiologically acceptable salts and/or N-oxides thereof, as inotropic agents, and to pharmaceutical formulations containing them. The invention also includes compounds of formula (I) (including physiologically acceptable salts and/or their N-oxides) perse, with the proviso that when n and m are both 1, and R2 is H, then when A' is nitrogen, A2 and A3 are both CH and R' is a 4-methoxy group, R3 is nota 7-methoxy group, and when A3 is nitrogen and A' and A2 are both CH and R' is a 4-methylsulphonyl group, R3 is not a 6-methoxy group, and processes for their preparation.

  本发明涉及式（I）化合物的用途 其中 n 是 1、2 或 3 m为0、1、2或3； A'、A2 和 A3 中的任一个是氮，另外两个是 CH； R'基团独立地选自下文(a)和(b)中规定的基团，即 (a) 氰基、羟基、式-S(O)xRa 的基团（其中 x 为 0、1 或 2，Ra 为 C1-4 烷基）和式-ORb 的基团（其中 Rb 为烯丙基或 C1-4 烷基，该烷基任选被一个或多个选自卤代、C1-4 烷氧基和式-S(O)xRa 的基团（其中 x 和 Ra 如上所定义）的基团取代；(b) C1-4 烷酰基、C1-4 烷酰氨基、2-甲基-1,3-二氧戊环-2-基、磺酰基、N-C1-4 烷基磺酰基、N, N-二-C1-4 烷基磺酰基、C1-4 烷基磺酰氧基、C1-4 烷基磺酰氨基、氨基磺酰氧基、N-C1-4 烷基氨基磺酰氧基、N、N-二-C1-4 烷基氨基磺酰氧基、脲基、3-C1-4 烷基脲基、3,3-二-C1-4 烷基脲基、氨基磺酰氨基、(C1-4 烷基氨基磺酰基)氨基、(二-C1-4 烷基氨基磺酰基)-氨基、羧基、羧酸衍生物（选自氨基甲酰基N-C1-4烷基氨基甲酰基、N，N-二-C1-4烷基氨基甲酰基、羧基卤化物、C1-4烷氧基羰基、羟基-C1-4烷氧基羰基和羟甲基）和式-ORC的基团，其中Re是具有1至4个碳原子的直链或支链脂肪族分子、可选择被一个或多个独立选自卤代、C1-4 烷氧基和式-S(O)xRa 的基团取代，其中 x 和 Ra 如上文所定义，但 R° 不是上文 Rb 所定义的基团； R2 选自氢、卤代、氨基、羟基、C1-4 烷基和 C1-4 烷氧基； R3 基团独立选自卤代、羧基、氨基、C1-4 烷基氨基羟基、C1-4 烷氧基、羟基-C1-4 烷氧基、C1-4 烷硫基和 C1-4 烷基磺酰氧基； 但当 R2 为氢且 m 为 0 或 m 为 1 且 R3 代表卤素时，则至少有一个 R'基团必须选自上述 (b)； 及其生理上可接受的盐和/或 N-氧化物，作为肌张力剂，以及含有它们的药物制剂。 本发明还包括式（I）化合物（包括生理学上可接受的盐和/或其 N-氧化物），但条件是当 n 和 m 均为 1 且 R2 为 H 时，当 A' 为氮、A2 和 A3 均为 CH 且 R' 为 4-甲氧基时，R3 不是 7-甲氧基；当 A3 为氮、A'和 A2 均为 CH 且 R' 为 4-甲磺酰基时，R3 不是 6-甲氧基，以及它们的制备工艺。
• SPITZER, WAYNE A.; VICTOR, FRANTZ; POLLOCK, G. DON; HAYES, J. SCOTT, J. MED. CHEM., 31, N8, 1988, 1590-1595
  作者：SPITZER, WAYNE A.、 VICTOR, FRANTZ、 POLLOCK, G. DON、 HAYES, J. SCOTT

  DOI：——

  日期：——
• Imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyrazines: the role of nitrogen position in inotropic activity
  作者：Wayne A. Spitzer、Frantz Victor、G. Don Pollock、J. Scott Hayes

  DOI：10.1021/jm00403a018

  日期：1988.8

  reaffirmed by the activity of our analogues. The biological equivalence of imidazo[4,5-b]pyridines with imidazo[1,2-a]pyrimidines and imidazo[4,5-c]pyridines with imidazo[1,2-a]pyrazines is demonstrated. Further, 2-[2-methoxy-4-(methylsulfenyl)phenyl]imidazo[1,2-a]pyrazine and 2-[2-methoxy-4-(methylsulfonyl)phenyl]-imidazo[1,2-a]pyrazine are potent inotropic agents both in vitro and in vivo.

  充血性心力衰竭是主要的医学问题，现有药物对其提供的益处有限。最近的新实验药物，包括咪唑并[4,5-b]-和咪唑并[4,5-c]吡啶，具有正性肌力和血管舒张性。这些化合物氮位置的细微变化已显示出会显着影响效能。我们合成了一系列咪唑[4,5-b]-和-[4,5-c]吡啶类似物，它们的咪唑氮原子位于桥头位置。我们的类似物的活性再次证明了[4,5-c]吡啶与[4,5-b]吡啶相比具有更好的正性肌力。证明了咪唑并[4,5-b]吡啶与咪唑并[1,2-a]嘧啶的生物等效性以及咪唑并[4,5-c]吡啶与咪唑并[1,2-a]吡嗪的生物学等效性。此外，2- [2-甲氧基-4-（甲基亚磺酰基）苯基]咪唑[1，
• Inotropic 2-arylimidazol[1,2-a]pyrimidines
  作者：P Barraclough、JW Black、D Cambridge、E Capon、MR Cox、D Firmin、VP Gerskowitch、H Giles、RC Glen、AP Hill、RAD Hull、R Iyer、D Kettle、WR King、MS Nobbs、P Randall、P Skone、S Smith、SJ Vine、CJ Wharton、MV Whiting

  DOI：10.1016/0223-5234(92)90004-k

  日期：1992.4

  A series of 2-arylimidazo[1,2-a]pyrimidines has been prepared and evaluated for inotropic activity. Three of these heterocycles. ether 19, sulphide 21 and mesylate 24 displayed more potent inotropic effects in vitro than isomazole. The in vivo inotropic potencies of 4'-mesylate 24 and 4'-carboxamido analogue 23 were similar to those of isomazole and sulmazole respectively. The effects of some 'A' and 'C' ring substituents on the inotropic activities of the imidazo[1,2-a]pyrimidines were different from those on the imidazopyridines. Nevertheless the inotropic potencies of several imidazo[1.2-a]pyrimidines were closer to those of their 1H-imidazo[4,5-b]pyridine isomers than to those of the corresponding isomazole analogues. Structure-activity relationships are discussed in detail.